Laboratory of Molecular Immunology, Department of Microbiology and Immunology, Rega Institute for Medical Research, KU Leuven, Leuven, Belgium.
Immunol Cell Biol. 2013 Jul;91(6):393-401. doi: 10.1038/icb.2013.15. Epub 2013 Apr 30.
Cytokines and chemokines represent two important groups of proteins that control the human immune system. Dysregulation of the network in which these immunomodulators function can result in uncontrolled inflammation, leading to various diseases including rheumatoid arthritis (RA), characterized by chronic inflammation and bone erosion. Potential triggers of RA include autoantibodies, cytokines and chemokines. The tight regulation of cytokine and chemokine production, and biological activity is important. Tumor necrosis factor-α (TNF-α) is abundantly present in RA patients' serum and the arthritic synovium. This review, therefore, discusses first the role and regulation of the major proinflammatory cytokine TNF-α, in particular the regulation of TNF-α production, post-translational processing and signaling of TNF-α and its receptors. Owing to the important role of TNF-α in RA, the TNF-α-producing cells and the dynamics of its expression, the direct and indirect action of this cytokine and possible biological therapy for RA are described.
细胞因子和趋化因子是控制人体免疫系统的两类重要蛋白质。这些免疫调节剂功能网络的失调可导致不受控制的炎症，从而导致各种疾病，包括类风湿关节炎（RA），其特征为慢性炎症和骨侵蚀。RA 的潜在诱因包括自身抗体、细胞因子和趋化因子。细胞因子和趋化因子产生和生物活性的严格调节非常重要。肿瘤坏死因子-α（TNF-α）在 RA 患者的血清和关节炎滑膜中大量存在。因此，本综述首先讨论了主要促炎细胞因子 TNF-α的作用和调节，特别是 TNF-α产生、翻译后加工和信号转导及其受体的调节。由于 TNF-α 在 RA 中的重要作用，以及 TNF-α 产生细胞及其表达的动态，描述了该细胞因子的直接和间接作用以及 RA 的可能生物治疗。
